nifurtimox and Parasitemia

People with Chagas disease may develop progressive and lethal heart conditions. Drugs to eliminate the parasite Trypanosoma cruzi (T cruzi) currently carry limited therapeutic value and are used in the early stages of the disease. Extending the use of these drugs to treat chronic chagasic cardiomyopathy (CCC) has also been proposed.. To assess the benefits and harms of nitrofurans and trypanocidal drugs for treating late-stage, symptomatic Chagas disease and CCC in terms of blood parasite reduction or clearance, mortality, adverse effects, and quality of life.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS databases on 12 November 2019. We also searched two clinical trials registers, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), on 3 December 2019.. We included randomised controlled trials (RCTs) assessing trypanocidal drugs versus placebo or no treatment for late-stage, symptomatic Chagas disease and CCC.. We conducted the reporting of the review according the standard Cochrane methods. Two review authors independently retrieved articles, performed data extraction, and assessed risk of bias. Any disagreements were resolved by a third review author. We contacted study authors for additional information.. We included two studies in this review update. One RCT randomly assigned 26 participants to benznidazole 5 mg/kg/day; 27 participants to nifurtimox 5 mg/kg/day; and 24 participants to placebo for 30 days. The second RCT, newly included in this update, randomised 1431 participants to benznidazole 300 mg/day for 40 to 80 days and 1423 participants to placebo. We also identified one ongoing study. Benznidazole compared to placebo At five-year follow-up, low quality of the evidence suggests that there may be a benefit of benznidazole when compared to placebo for clearance or reduction of antibody titres (risk ratio (RR) 1.25, 95% confidence interval (CI) 1.14 to 1.37; 1 trial; 1896 participants). We are uncertain about the effects of benznidazole for the clearance of parasitaemia demonstrated by negative xenodiagnosis, blood culture, and/or molecular assays due to very limited evidence. Low quality of the evidence suggests that when compared to placebo, benznidazole may make little to no difference in the risk of heart failure (RR 0.89, 95% CI 0.69 to 1.14; 1 trial; 2854 participants) and ventricular tachycardia (RR 0.80, 95% CI 0.51 to 1.26; 1 trial; 2854 participants). We found moderate quality of the evidence that adverse events increase with benznidazole when compared to placebo (RR 2.52, 95% CI 2.09 to 3.03; 1 trial; 2854 participants). Adverse effects were observed in 23.9% of patients in the benznidazole group compared to 9.5% in the placebo group. The most frequent adverse effects were: cutaneous rash, gastrointestinal symptoms, and peripheral polyneuropathy. No data were available for the outcomes of pathological demonstration of tissue parasites and quality of life. Nifurtimox compared to placebo Data were only available for this comparison for the outcome clearance or reduction of antibody titres, and we are uncertain about the effect due to very limited evidence. Regarding adverse events, one RCT mentioned in a general manner that nifurtimox caused intense adverse events, without any quantification.. There is insufficient evidence to support the efficacy of the trypanocidal drugs benznidazole and nifurtimox for late-stage, symptomatic Chagas disease and CCC.

Topics: Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Humans; Nifurtimox; Nitroimidazoles; Parasitemia; Placebos; Randomized Controlled Trials as Topic; Trypanocidal Agents; Trypanosoma cruzi

Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). It is endemic in Latin American countries outside the Caribbean. The current criterion for cure in the chronic phase of the disease is the negativization of at least two serological tests such as enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect hemagglutination assay (IHA). The serological evolution of treated subjects with chronic T. cruzi infection is variable. Treatment failure is indicated by a positive parasitological and/or molecular test (persistence of parasitemia).. To summarize the pattern of response to treatment of parasitological, molecular and serological tests performed during the follow-up of subjects with chronic T. cruzi infection.. Electronic searches in relevant databases and screening of citations of potentially eligible articles were accomplished. Organizations focusing on neglected infectious diseases were asked for help in identifying relevant studies. Included studies were randomized controlled trials (RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic infection who received trypanocidal treatment (benznidazole or nifurtimox) and were followed over time. The assessment of risk of bias was performed separately for each study design. The Cochrane Collaboration's tool and the guidelines developed by Hayden et al. were used. Two reviewers extracted all data independently. A third review author was consulted in case of discordant opinion. Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of positive parasitological and molecular tests and for negative serological tests were developed by using the lowess curve technique. Heterogeneity was measured by I2. The protocol was registered in PROSPERO, an international prospective register of systematic review protocols (Registration Number CRD42012002162).. Out of 2,136 citations screened, 54 studies (six RCTs and 48 cohort studies) were included. The smoothed curves for positive xenodiagnosis and positive polymerase chain reaction (PCR) were characterized by a sharp decrease at twelve month posttreatment. Afterwards, they reached 10-20% and 40% for xenodiagnosis and PCR, respectively. The smoothed curves for negative conventional serological tests increased up to 10% after 48 months of treatment. In the long-term, the rate of negativization was between 20% and 45%. The main sources of bias identified across cohort studies were the lack of control for confounding and attrition bias. In general, RCTs were judged as low risk of bias in all domains. The level of heterogeneity across included studies was moderate to high. Additional analysis were incomplete because of the limited availability of data. In this regard, the country of origin of study participants might affect the results of parasitological and molecular tests, while the level of risk of bias might affect serological outcomes. Subgroup analysis suggested that seronegativization occurs earlier in children compared to adults.. We acknowledge that there is a dynamic pattern of response based on parasitological, molecular and serological tests in subjects chronically infected with T. cruzi after treatment. Our findings suggest a trypanocidal effect in the long-term follow-up. Further research is needed to explore potential sources of heterogeneity and to conduct reliable subgroup analysis.

Topics: Adult; Antibodies, Protozoan; Chagas Disease; Child; Chronic Disease; Cohort Studies; Disease Progression; DNA, Protozoan; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Hemagglutination Tests; Humans; Nifurtimox; Nitroimidazoles; Parasitemia; Randomized Controlled Trials as Topic; Treatment Failure; Trypanocidal Agents; Trypanosoma cruzi; Xenodiagnosis

In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their "historical" boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas.

Topics: Adult; Blood Donors; Blood Safety; Chagas Disease; Donor Selection; Emigration and Immigration; Enzyme-Linked Immunosorbent Assay; Europe; Female; Global Health; Health Services Needs and Demand; Humans; Infant, Newborn; Latin America; Male; Mass Screening; Nifurtimox; Nitroimidazoles; North America; Parasitemia; Pregnancy; Pregnancy Complications, Infectious; Transfusion Reaction; Travel; Trypanocidal Agents; Trypanosoma cruzi

Chagas disease (ChD), caused by Trypanosoma cruzi, has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF. Treatment response was evaluated by clinical, parasitological, and serological after-treatment evaluation. A total of 289 patients were enrolled, of which 199 were children and 90 adults. At diagnosis, 89.6% of patients were asymptomatic. Overall, all symptomatic patients showed clinical improvement. At baseline, parasitemia was positive in 130 of 260 (50%) patients. All but one adult patient had cleared their parasitemia by the end of treatment. That patient was considered a treatment failure. Median follow-up time for children was 37.7 months, with an interquartile range of (IQR

Topics: Adult; Antibodies, Protozoan; Chagas Disease; Child; Cohort Studies; Humans; Nifurtimox; Nitroimidazoles; Parasitemia; Retrospective Studies; Trypanocidal Agents; Trypanosoma cruzi

Parasite persistence after acute infection with Trypanosoma cruzi is an important factor in the development of Chagas disease (CD) cardiomyopathy. Few studies have investigated the clinical effectiveness of CD treatment through the evaluation of cardiological events by long term follow-up of treated children. Cardiological evaluation in children is challenging since features that would be diagnosed as abnormal in an adult's ECG may be normal, age-related findings in a pediatric ECG trace. The objective was to evaluate cardiac involvement in patients with Chagas disease with a minimum follow-up of 6 years post-treatment.. A descriptive study of a cohort of pediatric patients with CD treated with benznidazole (Bz) or nifurtimox (Nf) was conducted. Children (N = 234) with at least 6 years post CD treatment followed at the Parasitology and Chagas Service, Buenos Aires Children's Hospital (Argentina) were enrolled. By convenience sampling, children who attended a clinical visit between August 2015 and November 2019 were also invited to participate for additional cardiovascular studies like 24-hour Holter monitoring and speckle-tracking 2D echocardiogram (STE). Benznidazole was prescribed in 171 patients and nifurtimox in 63 patients. Baseline parasitemia data was available for 168/234 patients. During the follow-up period, alterations in routine ECG were observed in 11/234 (4.7%, 95% CI [2-7.4%]) patients. In only four patients, with complete right bundle branch block (cRBBB) and left anterior fascicular block (LAFB), ECG alterations were considered probably related to CD. During follow-up, 129/130 (99%) treated patients achieved persistent negative parasitemia by qPCR. Also decrease in T.cruzi antibodies titers was observed in all patients and negative seroconversion occurred in 123/234 (52%) patients.. A low incidence of cardiological lesions related to CD was observed in patients treated early for pediatric CD. This suggests a protective effect of parasiticidal treatment on the development of cardiological lesions and highlights the importance of early treatment of infected children.. ClinicalTrials.gov NCT04090489.

Topics: Adult; Cardiology; Chagas Cardiomyopathy; Chagas Disease; Child; Humans; Nifurtimox; Nitroimidazoles; Parasitemia; Trypanocidal Agents; Trypanosoma cruzi

American trypanosomiasis or Chagas disease (CD) is a vector borne pathology caused by the parasite Trypanosoma cruzi (T. cruzi), which remains a serious global health problem. The current available treatment for CD is limited to two nitroderivatives with limited efficacy and several side effects. The rational design of ergosterol synthetic route inhibitors (e.g. CYP51 inhibitors) represents a promising strategy for fungi and trypanosomatids, exhibiting excellent anti-T.cruzi activity in pre-clinical assays. In the present work, we evaluate through different approaches (molecular docking, structure activity relationships, CYP51 inhibitory assay, and phenotypic screenings in vitro and in vivo) the potency and selectivity of a novel CYP51 inhibitor (compound 1) and its analogues against T.cruzi infection. Regarding anti-parasitic effect, compound 1 was active in vitro with EC

Topics: 14-alpha Demethylase Inhibitors; Animals; Chagas Disease; Mice; Molecular Docking Simulation; Parasitemia; Pyrazolones; Structure-Activity Relationship; Survival Rate; Thiazepines; Trypanosoma cruzi

Benznidazole and nifurtimox-treatments regimens currently used in human are supported by very limited experimental data. This study was designed to evaluate the time and dose dependence for efficacy of the most important nitroheterocyclic drugs in use for Chagas disease. In order to evaluate time dependence, Y strain-infected mice received benznidazole for a total of 1, 3, 7, 10, 20, and 40 days. Treatment courses of 3-10-day were effective in clearing parasitaemia and suppressing mortality, but parasitological cure was not achieved. Extending the treatments to 20 or 40 days clearly improved benznidazole efficacy. The 20-day treatment induced cure in 57.1% of Y strain infections (partially drug resistant) but failed to cure Colombian strain infections (full drug resistant), while the 40-day treatment resulted in cure of 100% of Y and 50% of Colombian strain infected mice. The increased cure rates in T. cruzi infected animals that received nifurtimox for 40 days confirm the relationship between the length of treatment and efficacy. An improvement in efficacy was observed with increasing benznidazole doses; cure was verified in 28.6% (75 mg/kg), 57.1% (100 mg/kg) and 80% (300 mg/kg). Overall, these nonclinical study data provide evidence that the efficacy of benznidazole is dose and time dependent. These findings may be relevant for optimizing treatment of human Chagas disease.

Topics: Animals; Chagas Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Mice; Nifurtimox; Parasitemia; Trypanocidal Agents; Trypanosoma cruzi

Although many Trypanosoma cruzi (T. cruzi) strains isolated from a wide range of hosts have been characterized, there is a lack of information about biological features from vertically transmitted strains. We describe the molecular and biological characteristics of the T. cruzi VD strain isolated from a congenital Chagas disease patient. The VD strain was typified as DTU TcVI; in vitro sensitivity to nifurtimox (NFX) and beznidazole (BZ) were 2.88 μM and 6.19 μM respectively, while inhibitory concentrations for intracellular amastigotes were 0.24 μM for BZ, and 0.66 μM for NFX. Biological behavior of VD strain was studied in a mouse model of acute infection, resulting in high levels of parasitemia and mortality with a rapid clearence of bloodstream trypomastigotes when treated with BZ or NFX, preventing mortality and reducing parasitic load and intensity of inflammatory infiltrate in skeletal and cardiac muscle. Treatment-induced parasitological cure, evaluated after immunossupression were 41% and 35% for BZ and NFX treatment respectively, suggesting a partial response to these drugs in elimination of parasite burden. This exhaustive characterization of this T. cruzi strain provides the basis for inclusion of this strain in a panel of reference strains for drug screening and adds a new valuable tool for the study of experimental T. cruzi infection.

Topics: Animals; Brain; Chagas Disease; Chlorocebus aethiops; Disease Models, Animal; DNA, Protozoan; Female; Heart; Humans; Infant; Infectious Disease Transmission, Vertical; Inhibitory Concentration 50; Male; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Myocardium; Nifurtimox; Nitroimidazoles; Parasitemia; Random Allocation; Trypanocidal Agents; Trypanosoma cruzi; Vero Cells

During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX) were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4-6 weeks old) infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day) and/or nifurtimox (NFMX; 100 mg/kg/day). Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days), while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox.

Topics: Animals; Chagas Disease; Chlorocebus aethiops; Disease Models, Animal; Drug Therapy, Combination; Female; Heart; Malondialdehyde; Mice; Mice, Inbred BALB C; Myocardium; Nifurtimox; Organ Size; Parasitemia; Spleen; Trypanocidal Agents; Trypanosoma cruzi; Vero Cells; Xanthophylls

Trypanosomes from animals are potential pathogens for humans. Several human cases infected by Trypanosoma lewisi, a parasite of rats, have been reported. The number of these infections is possibly underestimated. Some infections were self-cured, others required treatment with drugs used in human African trypanosomosis. An in vitro evaluation of these drugs and fexinidazole, a new oral drug candidate, has been performed against T. lewisi in comparison with T. brucei gambiense. All have comparable activities against the two parasites. Suramin was not effective. In vivo, drugs were tested in rats immunosuppressed by cyclophosphamide. The best efficacy was obtained for fexinidazole, and pentamidine (15 mg/kg): rats were cured in 7 and 10 days respectively. Rats receiving nifurtimox-eflornithine combination therapy (NECT) or pentamidine (4 mg/kg) were cured after 28 days, while melarsoprol was weakly active. The identification of efficient drugs with reduced toxicity will help in the management of new cases of atypical trypanosomosis.

Topics: Animals; Eflornithine; Female; Humans; Immunocompromised Host; Inhibitory Concentration 50; Melarsoprol; Mice; Nifurtimox; Nitroimidazoles; Parasitemia; Pentamidine; Rats; Rats, Wistar; Suramin; Trypanocidal Agents; Trypanosoma lewisi; Trypanosomiasis

The present work aimed to investigate the curative effect of benznidazole (BZL) in combination with other patented drugs [nifurtimox (NFX), posaconazole (POS) or AmBisome(®) (AMB)] in mice acutely or chronically infected with either a BZL-susceptible (Tulahuen) or a BZL-partially-resistant (Y) strain of Trypanosoma cruzi. To appreciate the eventual advantage of such combinations, infected mice were treated for short durations (non-curative) of each individual treatment. Cure rates were determined by investigating blood parasites (microscopic examination) and parasite DNA (quantitative PCR) after submitting treated mice to immune suppression with cyclophosphamide. The results mainly suggest that shorter durations of treatment combining BZL and POS or NFX might cure mice acutely or chronically infected with the Tulahuen strain, whereas the combination of BZL with AMB does not have such an effect. Moreover, the association BZL+POS does not improve the curative effect of POS (all used for shorter durations) in infection with the Y strain. Shortening the duration of treatment whilst keeping a complete curative effect deserves interest in limiting adverse reactions due to dose-cumulative toxic effects of long treatment. Genotyping of the T. cruzi strain(s) infecting patients might also allow a better adaptation of individual therapeutic schedules, improving both the efficiency and safety of trypanocidal treatment. This preliminary experimental study should encourage further investigations to find the best combination of adequate drug concentrations and timing of treatment.

Topics: Amphotericin B; Animals; Chagas Disease; Disease Models, Animal; DNA, Protozoan; Drug Therapy, Combination; Female; Mice; Mice, Inbred BALB C; Nifurtimox; Nitroimidazoles; Parasite Load; Parasitemia; Real-Time Polymerase Chain Reaction; Treatment Outcome; Triazoles; Trypanocidal Agents; Trypanosoma cruzi

For a fourth approach of quinoxaline N,N'-dioxides as anti-trypanosomatid agents against T. cruzi and Leishmania, we found extremely active derivatives. The present study allows us to state the correct requirements for obtaining optimal in vitro anti-T. cruzi activity. Derivatives possessing electron-withdrawing substituents in the 2-, 3-, 6-, and 7-positions were the most active compounds. With regard to these features and taking into account their mammal cytotoxicity, some trifluoromethylquinoxaline N,N'-dioxides have been proposed as candidates for further clinical studies. Consequently, mutagenicity and in vivo analyses were performed with the most promising derivatives. In addition, with regard to the mechanism of action studies, it was demonstrated that mitochondrial dehydrogenases are involved in the anti-T. cruzi activity of the most active derivatives.

Topics: Animals; Chemistry, Pharmaceutical; Cyclic N-Oxides; Drug Design; Electrons; Humans; Inhibitory Concentration 50; Mice; Models, Chemical; Mutagenicity Tests; Parasitemia; Quinoxalines; Toxicity Tests; Trypanocidal Agents; Trypanosoma cruzi

5-arylethenylbenzofuroxan derivatives with high in vitro anti-Trypanosoma cruzi activity were studied in vivo using acute murine models of Chagas' disease. The selected compounds, as pure isomeric forms, 1, 2, 3 and 4, or as equimolecular mixture of geometric isomers, 1:2, 3:4, 5:6 were studied against different T. cruzi strains. Consequently, Tulahuen 2 strain, Colombiana strain (resistant to Nifurtimox and Benznidazole), and two different wild strains, one isolated from the wild reservoir Didelphis marsupialis and another one from Uruguayan patients, were selected. No relevant signs of in vivo toxicity were observed with the benzofuroxans orally administered. Compound 1 and the mixture of isomers 1:2 were the best for treating infection against the four studied strains.

Topics: Acute Disease; Animals; Antibodies, Protozoan; Benzoxazoles; Chagas Disease; Disease Models, Animal; Female; Mice; Parasitemia; Treatment Outcome; Trypanosoma cruzi

In the present work we show that acute infection of C3H mice with the CL strain of Trypanosoma cruzi is characterized by an exponential growth of parasites and high mortality accompanied by anemia, thrombocytopenia, leukopenia, and bone marrow hypoplasia. Administration of nifurtimox, a trypanocydal drug currently in clinical use at different days postinfection, modulates parasitemia and prevents mortality. More importantly, none of blood and bone marrow alterations were observed in nifurtimox-treated animals when treatment was initiated early in infection, one or seven days postinoculation. The bone marrow alterations were characterized by a decrease in the total number cells as well in the number of megakaryoblasts and erythroblasts. Transfer experiments of bone marrow cells from infected mice to noninfected lethally irradiated recipients revealed a poor marrow-repopulating activity. The colony forming units-spleen assay confirmed the depression of committed clonal progenitors cells and revealed a decreased number of granulocyte/macrophage, megacariocyte and erythrocyte colonies. In summary, this is the first report showing that acute T. cruzi infection results in profound alterations of the hematopoietic system and that these alterations can be prevented by nifurtimox treatment.

Topics: Anemia; Animals; Blood Cell Count; Bone Marrow; Chagas Disease; Female; Hematopoietic Stem Cells; Leukopenia; Mice; Mice, Inbred C3H; Nifurtimox; Parasitemia; Thrombocytopenia; Trypanocidal Agents; Trypanosoma cruzi

Forty 8-aminoquinolines (a chemical class with members having some activity against Trypanosoma cruzi infections) were evaluated for their effectiveness in reducing the 14-day parasitaemias of 4-6 week-old, female, albino mice infected with a Brazilian strain of T. cruzi. Six of the compounds were more active or as active as the reference drug, nifurtimox, and one was > 13-fold as efficacious. Certain members of the series tested warrant further evaluation.

Topics: Aminoquinolines; Animals; Antiparasitic Agents; Chagas Disease; Drug Evaluation, Preclinical; Female; Mice; Nifurtimox; Parasitemia

The diagnostic and clinical aspects of congenital Chagas' disease were studied in 71 children in Buenos Aires. The children's ages ranged from 2 days to 10 years. In infants < 6 months old, the disease was diagnosed by detection of Trypanosoma cruzi in the blood; the microhematocrit test was positive in 38 (97.4%) of 39 cases. This test was the fastest and most reliable diagnostic method in this group, whereas two conventional serological methods were useful in children > or = 6 months of age. Forty-six (64.8%) of the 71 children had no clinical signs of infection. The clinical sign most frequently documented was hepatomegaly (18.3%). Three children were coinfected with human immunodeficiency virus; the latter infection was severe in two instances. Nifurtimox (10-15 mg/[kg.d] for 2 months) was used for parasiticidal treatment, and use of this drug resulted in mild adverse effects.

Topics: Animals; Antibodies, Protozoan; Argentina; Chagas Disease; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Nifurtimox; Parasitemia; Pregnancy; Serologic Tests; Trypanocidal Agents; Trypanosoma cruzi